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排序方式: 共有54条查询结果,搜索用时 15 毫秒
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Leigh Ford Erin Tay Tri-Hung Nguyen Hywel D. Williams Hassan Benameur Peter J. Scammells Christopher J. H. Porter 《RSC advances》2020,10(22):12788
Lipid based formulations (LBFs) are extensively utilised as an enabling technology in drug delivery. The use of ionic liquids (ILs) or lipophilic salts (LS) in drug delivery has also garnered considerable interest due to unique solubility properties. Conversion of active pharmaceutical ingredients (API) to ILs by pairing with an appropriately lipophilic counterion has been shown to decrease melting point of the salt complex and improve solubility in LBFs. However, the relationship between the structure of the counterion, the physicochemical properties of the resulting salts and solubility in LBFs has not been systematically explored. This study investigates the relationship between alkyl sulfate counterion structure and melting temperature (Tm or Tg) in addition to LBF solubility, utilizing cinnarizine and lumefantrine as model weakly basic APIs. Three series of structurally diverse alkyl sulfate counterions were chosen to probe this relationship. Pairing cinnarizine and lumefantrine with a majority of these alkyl sulfate counterions resulted in a reduction in melting temperature and enhanced solubility in model medium chain and long chain LBFs. The chain length of the alkyl sulfate plays a crucial role in performance, and consistently branched alkyl sulfate counterions perform better than straight chain alkyl sulfate counterions, as predicted. Most interestingly, trends in counterion performance were found to be consistent across two APIs with disparate chemical structures. The findings from this study will facilitate the design of counterions which enhance solubility of ionisable drugs and unlock the potential to develop compounds previously restrained by poor solubility.Structure/property relationship of API IL counterions and salt physicochemical properties are investigated, the results highlight the complex interplay involved. 相似文献
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Estelle J.A. Suys Dallas B. Warren Anna C. Pham Cameron J. Nowell Andrew J. Clulow Hassan Benameur Christopher J.H. Porter Colin W. Pouton David K. Chalmers 《Journal of pharmaceutical sciences》2019,108(1):193-204
Polyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6DBW and 2016H66 force field parameters for polyethoxylate chains. To compare the computational models to experimental measurements, we investigated the phase behavior of KOL using nephelometry, dynamic light scattering, cross-polarized microscopy, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The potential for digestion of KOL was also evaluated using an in vitro digestion experiment. We found that the size and spherical morphology of the KOL colloids at low concentrations was reproduced by the MD models as well as the growing interactions between the aggregates to from rod-like structures at high concentrations. We believe that this model reproduces the phase behavior of KOL relevant to drug absorption and that it can be used in whole formulation simulations to accelerate the formulation development. 相似文献
4.
Mahi M Amil T Chaouir S Hanine A Benameur M 《Journal of neuroradiology. Journal de neuroradiologie》2001,28(4):244-248
Radiological, computed tomography and magnetic resonance imaging findings in a case of spinal hydatidosis are reported. 相似文献
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William T. Hu J. Christina Howell Tugba Ozturk Karima Benameur Leda C. Bassit Richard Ramonell Kevin S. Cashman Shama Pirmohammed John D. Roback Vincent C. Marconi Irene Yang Valerie V. Mac Daniel Smith Ignacio Sanz Whitney Wharton F. Eun-Hyung Lee Raymond F. Schinazi 《Emerging infectious diseases》2020,26(12):2974
Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19. 相似文献
8.
Higher prevalence of cortical lesions observed in patients with acute stroke using high-resolution diffusion-weighted imaging 总被引:1,自引:0,他引:1
Benameur K Bykowski JL Luby M Warach S Latour LL 《AJNR. American journal of neuroradiology》2006,27(9):1987-1989
Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30 seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR], 256 seconds) having increased spatial resolution and signal to noise and decreased eddy current artifact in 42 patients with acute ischemic stroke. Total lesion volumes were similar; however, twice as many lesions were identified on DWI-HR, predominately in cortical gray matter. Modest improvements to imaging resulted in increased conspicuity, potentially affecting diagnosis, suspected pathogenic mechanism, and therapeutic decision. 相似文献
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Imaging features of CNS tuberculosis 总被引:1,自引:0,他引:1
Semlali S El Kharras A Mahi M Hsaini Y Benameur M Aziz N Chaouir S Akjouj S 《Journal de radiologie》2008,89(2):209-220
CNS tuberculosis remains relatively frequent in endemic regions. Both CT and MRI are valuable for diagnosis. Even though non-specific, MRI including diffusion-weighted imaging and proton spectroscopy is more sensitive than CT for detection of some lesions. The purpose of this paper is to illustrate the imaging features of CNS tuberculosis. 相似文献
10.
Dallas B. Warren Emma McPhee Woldeamanuel A. Birru Hassan Benameur David K. Chalmers Colin W. Pouton 《Journal of pharmaceutical sciences》2019,108(1):205-213
An iconic textbook that pharmaceutical scientists encounter in undergraduate courses is “Martin’s Physical Pharmacy and Pharmaceutical Sciences.” Within the chapter on Colloids, a figure indicates the location of solubilization of molecules within spherical, nonionic surfactant micelles. The surfactant consists of polyethylene glycol (PEG) hydrophilic headgroups and alkane chains for the hydrophobic tail. The figure shows benzene and toluene within the alkane core, salicylic acid (2-hydroxybenzoic acid) at the interface between the core and PEG chains, and then para-hydroxybenzoic acid (4-hydroxybenzoic acid) located between the PEG chains. Molecular dynamics simulations of octaethylene glycol monododecyl ether micelles were performed with a series of probe molecules, including those within the Martin’s figure, to determine their solubilization location. Relative placement of molecules within the micelle was correct; however, some specifics were different. In particular, benzene and toluene are excluded from the core, and 4-hydroxybenzoic acid prefers to maintain contact with the core. A series of molecules containing 6 carbon atoms were also studied to determine the effects of cyclization (moves out of core), polar functionalization (anchored to interface), and aromatization (excluded from central core). Molecular dynamics was found to be a useful tool for gaining insight into interactions important in solubilization of molecules. 相似文献